Department of Nephrology, Shenzhen Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen, China.
Diabetes Res Clin Pract. 2013 Apr;100(1):85-95. doi: 10.1016/j.diabres.2013.01.012. Epub 2013 Feb 4.
The present study was undertaken to investigate the therapeutic effect and underlying mechanisms of lumbrokinase on diabetic nephropathy.
Type I diabetes was induced in male Sprague-Dawley rats via intraperitoneal injection of Streptozotocin (STZ). Lumbrokinase was administered to the diabetic rats at a dose of 600,000 U/kg body weight by gavage. As a positive control, perindopril, an angiotensin-converting enzyme inhibitor (ACEI), was given to diabetic rats at a dose of 4 mg/kg body weight. Following 12 weeks treatment, we measured the creatinine clearance rate (Ccr), urinary albumin excretion (UAE) and kidney injury scores. In addition, the expression of collagen IV, MMP-2 and MMP-9 in renal tissue was evaluated.
The diabetic rats developed proteinuria, glomerulosclerosis, tubulointerstitial fibrosis and a marked increase of renal cortical collagen IV. In contrast, MMP-2 and MMP-9 were significantly reduced in the renal cortex of diabetic rats. Interestingly, lumbrokinase treatment markedly reduced the proteinuria and improved the glomerulosclerosis and tubulointerstitial fibrosis in diabetic rats. The induction of collagen IV and the down-regulation of MMP-2 and MMP-9 was significantly attenuated by lumbrokinase. All these beneficial effects of lumbrokinase were comparable to the ACEI group.
Lumbrokinase treatment attenuated diabetic nephropathy in rats, possibly through increasing the activity of MMPs and the subsequent degradation of extracellular matrix.
本研究旨在探讨蚓激酶对糖尿病肾病的治疗作用及其机制。
雄性 Sprague-Dawley 大鼠经腹腔注射链脲佐菌素（STZ）诱导 I 型糖尿病。蚓激酶以 600,000 U/kg 体重的剂量通过灌胃给予糖尿病大鼠。作为阳性对照，血管紧张素转换酶抑制剂（ACEI）培哚普利以 4mg/kg 体重的剂量给予糖尿病大鼠。治疗 12 周后，我们测量了肌酐清除率（Ccr）、尿白蛋白排泄率（UAE）和肾脏损伤评分。此外，还评估了肾脏组织中胶原 IV、MMP-2 和 MMP-9 的表达。
糖尿病大鼠出现蛋白尿、肾小球硬化、肾小管间质纤维化和皮质胶原 IV 明显增加。相比之下，糖尿病大鼠肾脏皮质中的 MMP-2 和 MMP-9 显著减少。有趣的是，蚓激酶治疗显著减少了糖尿病大鼠的蛋白尿，并改善了肾小球硬化和肾小管间质纤维化。蚓激酶明显减弱了胶原 IV 的诱导和 MMP-2 和 MMP-9 的下调。蚓激酶的所有这些有益作用均与 ACEI 组相当。
蚓激酶治疗可减轻大鼠糖尿病肾病，可能通过增加 MMP 的活性和随后的细胞外基质降解。
